Contact PD/PI: Lechner, William V SUMMARY Smoking remains the leading cause of preventable death in the United States, and current first-line treatments leave the majority of tobacco dependent individuals unable to quit. The inability to quit despite motivation to do so, is thought to result in part, from self-control failure. Working memory (WM) deficits contribute to imbalanced self-control and allow automatic impulses to drive behavior. Thus, WM plays a critical role in addictive behavior, and is particularly relevant to smoking. Indeed, a strong link between WM and smoking has been established in the literature; most notably, degree of WM impairment and deficits in activation in associated brain regions predict time to relapse, and WM moderates the relationship between craving and relapse. Given these insights, researchers have been examining interventions that may target WM including WM training (WMT) and repetitive Transcranial Magnetic Stimulation (rTMS). WMT involves taxing this executive function repeatedly over time and has shown positive preliminary results in improving measures of self-control and reducing consumption of addictive substances. Similarly, rTMS, a non-invasive brain stimulation procedure that stimulates neuronal tissues and increases cortical excitability, has been shown to increase WM capacity and reduce craving and consumption of several addictive substances including nicotine. While these interventions have demonstrated initial promise in affecting addictive behaviors, the magnitude and durability of their effects may be limited. Recently, researchers have posited ? but not yet empirically tested ? that WMT administered in combination with rTMS may result in an additive or supra-additive effect in treating addictive processes. This is highly significant; the clinical utility of rTMS over current first line treatments may be limited if factors with potential to enhance its effectiveness are not examined. Given these recent advances in the literature, the primary objective of the proposed study is to evaluate the individual and combined effects of Working Memory (WM) training and repetitive Transcranial Magnetic Stimulation (rTMS) on WM performance and smoking behaviors as well as critical mediators of these effects. These aims will be examined in a sample of tobacco dependent adults (N=130) utilizing a 2x2 factorial experimental design including four groups (WMT+rTMS, sham WMT+rTMS, WMT+sham TMS, and sham WMT+sham rTMS) capable of isolating independent and combined effects of WMT and rTMS. Baseline assessment will include a smoking analogue task with high translational value, followed by 10 sessions of working memory training over two weeks prior to the initiation of rTMS. rTMS will consist of 10 sessions over two weeks with 10 Hz stimulation (2000 pulses per session) applied over the left DLPFC, with working memory training co-occurring with stimulation. The study will assess neurocognitive, psychological, and behavioral mediators at multiple time points between baseline and final outcome assessment. Project Summary/Abstract Page 7